MECHANISMS OF NONSTERILIZING IMMUNITY IN MALARIA

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The overall goal of the proposed research is to investigate the biology of T lymphocytes activated by murine plasmodia with the aim of understanding how these cells participate in protective immune response during malaria. In particular, attention will be focused on antibody-independent cell mediated protective immune responses leading to parasite death or growth inhibition. Antigen-specific protective T-cell clones including CTR2.1 and others to be developed against P. chabaudi adami as well as against P. vinckei petteri and B. microti utilizing in vitro culture techniques will be tested for their protective activity in vivo against homologous and heterologous parasites by means of adoptive transfer into histocompatible nude mice. Protective and nonprotective T-cell clones will be characterized according to surface antigens, lymphokine production, antigenic specificity, and trafficking in an effort to identify characteristics distinctive of protective cloned T cells. In addition, experiments will be undertaken to characterize the biological function of protective T-cell clones both in vitro and in vivo in order to determine whether they kill parasites through the release of specific mediators or activate additional cell types in a common pathway of resistance. Efforts will also be made to determine whether the function of malaria- protective cloned T cells can be modulated by T cells displaying antigen-specific suppressive activity.